PB2164: PROGNOSTIC IMPACT OF ONCOGENE DEK IN DIFFUSE LARGE B-CELL LYMPHOMA
Authors: R. Alonso Alonso, M. Rodríguez, L. M. Privette Vinnedge, J. Serrano, Y. Jiménez de las Pozas, S. G Pedrero, D. Laínez, A. García Raso, J. M. Alonso Dominguez, A. López García, R. Córdoba, M. A. Piris, P. Llamas Sillero, J. Sánchez García, J. Serrano Lopez
Journal: HemaSphere (2022)

Background: Diffuse Large B-Cell Lymphoma (DLBCL) is an aggressive hematologic malignancy that represents 25-30% of non-Hodgkin’s lymphomas (NHL). DLBCL can be subdivided according to its cell of origin (COO) into germinal center B-cells (GCB), activated B-cell (ABC) and non-classifiable (NC) subtypes, with the ABC subtype having the worst prognosis. Previous studies by our group describe that in normal hematopoiesis DEK knockout mice had fewer mature B cells than controls. In some hematological neoplasms, DEK is considered a biomarker for normal and malignant plasma cells, such as in Multiple Myeloma and Chronic Lymphocytic Leukemia, where the use of fludarabine and Nutlin-3 decreased DEK expression levels significantly in those patients with normal TP53 function. Aims: Since the DEK oncogene has not been studied in DLBCL previously, the aim of this work is to study the prognostic impact of DEK mRNA expression levels in DLBCL. Methods: This study included a total of 66 FFPE samples from DLBCL patients, 41 were collected from the HURS and 25 from the HUFJD. The COO categorization was carried out on the Nanostring platform applying the Lymphoma subtyping test(LST) algorithm. Using qRT-PCR, we quantified DEK gene expression and the median expression was used as the cut-off point. p53 status was analyzed by immununohistochemistry using an anti-TP53 antibody (clone: DO-7). Analysis statistics: χ2 test to study associations. Correlation analyses were obtained by GEPIA. Kaplan-Meier to calculate survival curves. Multivariate analysis by Cox regression and Binary logic regression. Results: Mean patient age was 68.5 years (range 40-89 years). 29 patients were classified as GCB subgroup, 22 patients in ABC and 15 as NC. High levels of DEK expression (DEKHigh) were found in 38 patients, and low expression levels in 28 (DEKLow). TP53 protein was positive in 15 patients, negative in 25 and not studied in 26. All p53+ patients had high DEK levels (TP53+/DEKHigh); however, 16 of the TP53- patients had low DEK expression levels (TP53-/DEKLow). GCB subgroup had a significant association between p53 status and DEK expression. However, in the ABC subgroup, in addition to the association between DEK and p53, significant associations with stage, response to treatment, relapse and death were also found. DEK expression correlates with the ABC subtype markers IRF4 and LIMD1 (R=0.58), BCL family protein markers (BCL6/BCL2)(R=0.49 and 0.41), poor prognosis markers (MYC/CD5)(R=0.54 and 0.31), and with nuclear transcription factor RELA(R=0.65), but does not correlate with NFkB pathway activation markers (IL2/IL6) and GCB subtype. DEK expression also correlated with TP53 (R=0.59). Kaplan-Meier survival curves show lower overall survival in DEKHigh patients in the entire cohort. This association was significant by the Log Rank test (p=0.02). Overall survival (OS) in ABC patients was significantly lower in DEKHigh and TP53+/DEKHigh patients (p=0.005 and p=0.05 respectively); however, no significance was found in the GCB subgroup. Finally, DEKHigh at diagnosis was an independent marker to predict standard treatment response (OR=4.17, IC=1.18-14.73) and a risk factor for OS (HR=3.39, IC=1.21-9.52). Summary/Conclusion: Patients diagnosed with DLBCL with high levels of DEK oncogene expression have worse responses to treatment and lower overall survival compared to patients with lower levels of expression. These associations were especially strong in the ABC subtype, where DEK expression also correlated with poor prognosis markers and was an independent predictor of treatment response.